The most widely used analgesic and anti-inflammatory drug is aspirin, which remains the drug of choice for the treatment of arthritis and common aches and pains. Unfortunately, the use of aspirin, the chemical name of which is acetylsalicylic acid, can be accompanied by undesirable side effects. These side effects include gastric mucosal irritation, gastric distress and intolerance and are due to the acidic character of aspirin and to its poor water solubility. Once ingested, aspirin tablets disintegrate, leaving insoluble particles which lodge in and irritate the gastric mucosa. Because of the irritation caused by conventional aspirin, many individuals taking aspirin suffer gastric distress. Acetaminophen (as present in Tylenol, Datril etc.) is sometimes taken instead of aspirin to avoid gastric distress, but this compound is ineffective in reducing inflammation. Arthritic patients who suffer from inflammation but cannot tolerate aspirin must thus turn to other, more dangerous drugs.
In efforts to overcome the shortcomings of ordinary aspirin, a number of approaches have been explored. There are available today a number of buffered aspirin compositions such as Bufferin, Excedrin and Anacin. These compositions neutralize some gastric acid but do not eliminate the basic problem--insoluble aspirin particles form which persist in causing gastric mucosal irritation.
Aspirin could be formulated into enteric coated tablets, but such formulations would merely shift the locus of irritation to the duodenal mucosa and to other regions of the gastrointestinal tract, where the tablets would disintegrate.
More effective are compositions similar to Alka-Seltzer, which produce a soluble form of aspirin upon contact with water that is readily assimilated by the body and which, therefore, does not cause localized irritation. But the way such compositions accomplish this objective is not very efficient. Large quantities of sodium bicarbonate are employed which may exceed the weight of the aspirin contained by a factor of ten or more. The preparations are also costly for the analgesic dose they provide, and they can produce distending quantities of gas. As a result, they are practically never used by arthritic patients or by individuals with chronic pain or inflammation.
The sodium salt derivative of aspirin produced when Alka-Seltzer dissolves in water would prove beneficial if it could be isolated free of excess bicarbonate salt and formulated into a convenient dosage form, but severe problems of stability make the attainment of both of these objectives difficult. The preparation of sodium aspirin in aqueous solution, is an easy task, but removal of the water to yield useable solid crystals is difficult. The acetate group of sodium aspirin tends to hydrolyze to produce salicylic acid during the dehydration of the compound. Granular plate-like crystals of sodium aspirin have been produced by Galat (U.S. Pat. No. 3,985,792) in a process involving precipitation of the compound from aqueous solution and removal of the water of hydration. But, formulation of the pure, anhydrous compound into a useable dosage form presents further, severe stability problems.
The typical tablet formulation consists of an active ingredient, a bulking agent, a binder, a lubricant and a disintegrant. The latter ingredient is generally needed to ensure rapid decomposition of the tablet and hence ready availability of the active ingredient. Unfortunately, when sodium aspirin is the active ingredient in such a composition, it undergoes unacceptably rapid degradation to salicylic acid.